α-硫辛酸在衰老大鼠听皮层线粒体氧化损伤中的作用

The Role ofα-lipoic Acid in Mitochondrial Oxidative Damage in Auditory Cortex of Aging Rats

目的研究抗氧化剂α-硫辛酸(α-lipoic acid,α-LA)对衰老大鼠听皮层线粒体氧化损伤的影响。方法4周龄雄性SD大鼠48只,分为3组(n=16):①对照组(NS):腹腔注射生理盐水500mg.(kg.d)-18周后,腹腔注射生理盐水40mg.(kg.d)-18周;②衰老组(D-gal):腹腔注射D-半乳糖500mg.(kg.d)-18周后,腹腔注射生理盐水40mg.(kg.d)-18周;③干预组(α-LA):腹腔注射D-半乳糖500mg.(kg.d)-18周后,腹腔注射α-硫辛酸40mg.(kg.d)-18周。完成干预后,麻醉后处死大鼠,观察听皮层神经元超微结构,检测含量、线粒体膜电位(mitochondrial membrane potential,MMP)水平、H2O2含量、总超氧化物歧化酶(Total superoxide dismutase,T-SOD)表达与8-羟基-2-脱氧鸟苷(8-hydroxy-2-deoxyguanosine,8-OHdG)含量。结果衰老组大鼠听皮层T-SOD表达、含量与MMP水平均明显低于对照组,而H2O2含量与8-OHdG含量明显高于对照组。α-硫辛酸干预后,大鼠听皮层T-SOD表达、ATP含量与MMP水平明显增加,而H2O2含量与8-OHdG含量明显降低。结论α-硫辛酸可减轻衰老过程中听皮层线粒体氧化损伤。

Objective To study the effect of antioxidantα-lipoic acid(α-LA)on mitochondrial oxidative damage of auditory cortex in aged rats.Methods Forty eight 4-weeks-old male SD rats were divided into a control group(NS,intraperitoneal injection of normal saline at 500 mg/kg/d for 8 weeks followed by intraperitoneal injection of normal saline at 40 mg/kg/d for another 8 weeks),an aging group(D-gal,intraperitoneal injection of D-galactose at 500 mg/kg/d for 8 weeks followed by intraperitoneal injection of normal saline at 40 mg/kg/d for another 8 weeks),and an intervention group(α-LA.intraperitoneal injection of D-galactose 500 mg/kg/d for 8 weeks followed by intraperitoneal injection ofα-lipoic acid at 40 mg/kg/d for another 8 weeks)(n=16 in each group).At the end of intervention,rats were sacrificed under anesthesia.Ultrastructure of auditory cortex neurons was examined for the level of ATP,mitochondrial membrane potential(MMP),H2O2,total superoxide dismutase(T-SOD)expression and 8-hydroxy-2-deoxyguanosine(8-OHdG).Results Levels of T-SOD,ATP and MMP in the aging group were significantly lower while the content of H2O2 and 8-OHdG significantly higher than in the control group.Withα-lipoic acid intervention,T-SOD expression,ATP content and MMP level increased,while the content of H2O2 and 8-OHdG decreased,significantly.Conclusionα-lipoic acid can decrease aging-related mitochondrial oxidative damage in the auditory cortex.